The proposal investigates the interplay of host and viral factors involved in the development of the immune response to Respiratory Syncitial Virus (RSV) infection in mice. Preliminary data indicate that RSV-specific CD8+ T lymphocytes play an important regulatory role in directing the differentiation of RSV-specific memory CD4+ T lymphocytes into Th-1 or Th-2 effectors. In Aim 1, an in vitro model will be developed to investigate the role of CD8+ T cells in the development of effector CD4+ T cells. In particular, the roles of soluble and cell associated CD8 T lymphocyte gene products in driving Th-1 versus Th-2 responses to the RSV-G glycoprotein will be investigated. In Aim 2, subdominant Th epitopes will be identified to examine their contribution to Th-2 effector function and pulmonary eosinophil accumulation in response to RSV challenge. Finally in Aim 3, a combination of selective breeding and chromosomal DNA marker analysis will be used to identify host genetic loci that regulate the response of CD4+ T lymphocytes to RSV infection. These studies will provide new and potentially important information on the interaction of CD4+ and CD8+ T cells in the clearance of RSV infection. This information will be important for the development of an effective RSV vaccine.